title: The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation.
abstract: In the present study, we have analyzed the pattern of cytokines expressed by two independent dendritic cell (DC) subpopulations generated in vitro from human cord blood CD34+ progenitors cultured with granulocyte-macrophage CSF and TNF-alpha. Molecularly, we confirmed the phenotypic differences discriminating the two subsets: E-cadherin mRNA was only detected in CD1a+-derived DC, whereas CD68 and factor XIIIa mRNAs were observed exclusively in CD14+-derived DC. Semiquantitative reverse-transcriptase PCR analysis revealed that both DC subpopulations spontaneously expressed IL-1alpha, IL-1beta, IL-6, IL-7, IL-12 (p35 and p40), IL-15, IL-18, TNF-alpha, TGF-beta, macrophage CSF, and granulocyte-macrophage CSF, but not IL-2, IL-3, IL-4, IL-5, IL-9, and IFN-gamma transcripts. Both subpopulations were shown to secrete IL-12 after CD40 triggering. Interestingly, only the CD14+-derived DC secreted IL-10 after CD40 activation, strengthening the notion that the two DC subpopulations indeed represent two independent pathways of DC development. Furthermore, both DC subpopulations expressed IL-13 mRNA and protein following activation with PMA-ionomycin, but not with CD40 ligand, in contrast to IL-12 and IL-10, revealing the existence of different pathways for DC activation. Finally, we confirmed the expression of IL-7, IL-10, and IL-13 mRNA by CD4+ CD11c+ CD3- DC isolated ex vivo from tonsillar germinal centers. Thus, CD14+-derived DC expressing IL-10 and factor XIIIa seemed more closely related to germinal center dendritic cellsGCDC than to Langerhans cells.
authors.affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
authors.forename: B
authors.initials: B
authors.lastname: de Saint-Vis
authors.forename: I
authors.initials: I
authors.lastname: Fugier-Vivier
authors.forename: C
authors.initials: C
authors.lastname: Massacrier
authors.forename: C
authors.initials: C
authors.lastname: Gaillard
authors.forename: B
authors.initials: B
authors.lastname: Vanbervliet
authors.forename: S
authors.initials: S
authors.lastname: Aït-Yahia
authors.forename: J
authors.initials: J
authors.lastname: Banchereau
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Lebecque
authors.forename: C
authors.initials: C
authors.lastname: Caux
mesh_terms: D018949:Antigens, CD1 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000096:biosynthesis; D020382:Interleukin-18; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018949:Antigens, CD1; D018952:Antigens, CD34; D016207:Cytokines; D018793:Interleukin-13; D020382:Interleukin-18; D015851:Interleukin-7; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate